One type of treatment for patients having substantially impaired renal function, or kidney failure, is known as “dialysis”. Either blood dialysis (“hemodialysis”) or peritoneal dialysis (“PD”) methods may be employed. Both methods essentially involve the removal of toxins from body fluids and restoration of such body fluids by diffusion and/or convection by means of a dialysis solution.
Patients receiving hemodialysis typically utilize 75 to 200 liters of prepared dialysis solution three times a week. The largest ingredient in these solutions is water.
Conventionally, dialysis solutions for hemodialysis are prepared from separate concentrated solutions. For example, one concentrate, Preparation A, includes a mixture of varied salts, sugars and acids dissolved in water. Another concentrate, Preparation B, is made of sodium bicarbonate dissolved in water, and may also contain sodium chloride. The constituents must be kept separate until shortly before hemodialysis because of the tendency for insoluble precipitates to form in the combined solution.
Even in concentrated solutions, the Preparations A and B are themselves bulky and difficult to transport. Moreover, bicarbonate solutions such as Preparation B have a tendency to form carbon dioxide and alter the pH of their solution over extended periods of time, even if not mixed with other components. Another logistical problem with preparing dialysis solutions is the need to keep the solutions essentially free of bacteria and endotoxins.
In PD, the patient's peritoneal cavity is filled with a dialysis solution. The dialysis solution is generally formulated with a high concentration of the dextrose, as compared to body fluids, resulting in an osmotic gradient within the peritoneal cavity. The effect of this gradient is to cause body fluids, including impurities, to pass through the peritoneal membrane and mix with the dialysis solution. By draining the spent dialysis solution from the cavity, the impurities are removed.
In PD, the dialysis solution is administered directly into the patient's body, and it is thus important that the dialysis solution is sterile and maintains the correct proportions and concentrations of components. Conventionally, for PD, dialysis solutions are delivered to the site of administration in pre-mixed solutions.
Similar to dialysis solutions for hemodialysis, the dialysis solutions used in PD are not stable over time due to incompatibility of the components in these solutions. For example, dextrose has a tendency to caramelize in solution over time, and bicarbonate ions react undesirably with calcium and magnesium in solutions to form insoluble calcium carbonate or magnesium carbonate. Bicarbonate can also spontaneously decompose into carbon dioxide and water.
Significant research efforts have been spent on providing dry formulations of components that are subsequently mixed with a solvent, typically water, to form dialysis concentrates or dialysis solutions. The use of dry formulations in the form of powdery material has the potential of increasing shelf life, reduce the formation of possible degradation products, and reduce the weight and volume of the material that needs to be transported to and stored at the dialysis treatment sites.
However, there are difficulties in using dry formulations for preparation of dialysis concentrates and dialysis solutions.
One difficulty associated with the use of dry formulations is that certain components of the dry formulations are incompatible and therefore have to be stored separately. Some of the components, e.g. magnesium chloride, calcium chloride and glucose, typically bind water molecules, at least in their commonly used forms, while other components, e.g. NaCl, are hygroscopic. If the former component(s) releases water during storage, the latter component(s) may form lumps or cakes, and these lumps/cakes may be difficult to dissolve when preparing the dialysis solution. If bicarbonates and acids are mixed, gases may be formed in the presence of water. If glucose and acids are mixed and subject to non-dry conditions, the glucose may be degraded and discolored. These problems may be overcome by storing the different dry formulations in separate packages. Another way of dealing with these problems is to separate the dry formulations into compatible groupings, which are arranged to be physically separated within the package. Such packages are e.g. known from US2006/0115395, WO2007/144427 and WO2011/161064, and are designed to reduce the risk for incorrect composition of the dialysis solution due to incorrect handling.
It may also be important to design the package so as to prevent moisture from entering or leaving the package during storage and transport, for example to avoid that water enters the package from the outside to degrade the dry formulation or causing it to release gases, or to avoid that bound water is released from the dry formulation and leaves the package. To achieve an effective barrier against moisture transport, the wall thickness of the package may be increased or the package may be manufactured in a dedicated vapor barrier material. It is also possible to protect the package by a dedicated overwrap, e.g. a separate plastic film which is arranged around the package and attached by adhesive, tape or heat sealing, e.g. by so-called shrink wrapping. All of these solutions increase the cost for the package.
There are other design criteria for the package that may or may not be important, e.g. to make the package compact and easy to store, to make the package easy to handle when the dialysis solution is to be prepared, to make the package easy to manufacture, etc.
Although the foregoing discussion is given in relation to preparation of dialysis solutions, it is to be understood that corresponding problems and needs are equally and generally valid for the preparation of other types of medical solutions, such as replacement solutions, infusion solutions or nutritional solutions.